Is ELFN1 p.Pro50His (c.149C>A) pathogenic?

ELFN1 p.Pro50His (c.149C>A) is classified Pathogenic in ELFN1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-09-15). AlphaMissense: likely pathogenic (0.9648); Very rare (popmax 8.71e-05%, nfe); Associated with Dursun-Ozgul neurodevelopmental syndrome.

What condition is associated with ELFN1 p.Pro50His (c.149C>A)?

ELFN1 p.Pro50His (c.149C>A) is associated with Dursun-Ozgul neurodevelopmental syndrome (ClinVar).

How common is ELFN1 p.Pro50His (c.149C>A) in the general population?

ELFN1 p.Pro50His (c.149C>A) is very rare (popmax 8.71e-05%, nfe) (gnomAD).

What do computational predictors say about ELFN1 p.Pro50His (c.149C>A)?

AlphaMissense predicts likely pathogenic (score 0.9648) — an in-silico prediction, not a clinical call.

ELFN1 p.Pro50His

c.149C>A · VCV4083482

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9648 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.71e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt

Conditions

Dursun-Ozgul neurodevelopmental syndrome

Computational evidence

Protein change
AlphaMissense	0.9648	likely pathogenic ✓ concordant with ClinVar · top 10% in ELFN1
SaProt	LLR -12.15	damaging
⇒ AlphaMissense and SaProt both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 738 bp · p 3.5e-08 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.71e-05% European (non-Finnish) · 1/1,147,804 alleles

Overall 7.14e-05% 1/1,400,872 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ELFN1
Protein: p.Pro50His
Coding: c.149C>A
MANE Select: NM_001128636
Type: single nucleotide variant
Location: chr7:1744745 (GRCh38)
Gene constraint: LOEUF 1.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 5 PDB
Residue 50: a UniProt-annotated variant site (in donds; likely pathogenic; decreased localization to the cell membrane)

Full ELFN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Dursun-Ozgul neurodevelopmental syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ELFN1 p.Ala15fs Pathogenic/Likely pathogenic same condition
ELFN1 p.Ile43fs Pathogenic same condition
ELFN1 p.Val159del Pathogenic same condition
ELFN1 p.Val591fs Pathogenic same condition
ELFN1 p.Ala14= Benign/Likely benign ★★ same type
ELFN1 p.Ala796= Benign/Likely benign ★★ same type
ELFN1 p.Asp618= Likely benign ★★ same type
ELFN1 p.Cys196= Likely benign ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/elfn1-p-pro50his (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown